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Noninvasive and quantitative live imaging reveals a potential stress‐responsive enhancer in the failing heart
Author(s) -
Matsuoka Ken,
Asano Yoshihiro,
Higo Shuichiro,
Tsukamoto Osamu,
Yan Yi,
Yamazaki Satoru,
Matsuzaki Takashi,
Kioka Hidetaka,
Kato Hisakazu,
Uno Yoshihiro,
Asakura Masanori,
Asanuma Hiroshi,
Minamino Tetsuo,
Aburatani Hiroyuki,
Kitakaze Masafumi,
Komuro Issei,
Takashima Seiji
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-245522
Subject(s) - enhancer , stress (linguistics) , medicine , cardiology , biology , genetics , philosophy , transcription factor , gene , linguistics
Recent advances in genome analysis have enabled the identification of numerous distal enhancers that regulate gene expression in various conditions. However, the enhancers involved in pathological conditions are largely unknown because of the lack of in vivo quantitative assessment of enhancer activity in live animals. Here, we established a noninvasive and quantitative live imaging system for monitoring transcriptional activity and identified a novel stress‐responsive enhancer of Nppa and Nppb , the most common markers of heart failure. The enhancer is a 650‐bp fragment within 50 kb of the Nppa and Nppb loci. A chromosome conformation capture (3C) assay revealed that this distal enhancer directly interacts with the 5'‐flanking regions of Nppa and Nppb. To monitor the enhancer activity in a live heart, we established an imaging system using the firefly luciferase reporter. Using this imaging system, we observed that the novel enhancer activated the reporter gene in pressure overload‐induced failing hearts (failing hearts: 5.7±1.3‐fold; sham‐surgery hearts: 1.0±0.2‐fold; P <0.001, repeated‐measures ANOVA). This method will be particularly useful for identifying enhancers that function only during pathological conditions.—Matsuoka, K., Asano, Y., Higo, S., Tsukamoto, O., Yan, Y., Yamazaki, S., Matsuzaki, T., Kioka, H., Kato, H., Uno, Y., Asakura, M., Asanuma, H., Minamino, T., Aburatani, H., Kitakaze, M., Komuro, I., and Takashima, S. Noninvasive and quantitative live imaging reveals a potential stress‐responsive enhancer in the failing heart. FASEB J. 28, 1870–1879 (2014). www.fasebj.org